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High-grade Prostatic Intraepithelial Neoplasia (high-grade + prostatic_intraepithelial_neoplasia)
Selected AbstractsFlutamide reduced prostate cancer development and prostate stem cell antigen mRNA expression in high grade prostatic intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Zhao Zhigang Abstract High-grade prostatic intraepithelial neoplasia (HGPIN) appears to represent an ideal target for chemoprevention of prostate cancer (PCa). HGPIN responds to androgen ablation and has prostate stem cell antigen (PSCA) mRNA expression. One hundred and seventy two patients with isolated HGPIN were randomized in a double-blind manner to receive flutamide 250 mg/day (86 cases) or a placebo (86 cases) for 12 months and were rebiopsied at 12 and 60 months. PSCA mRNA expression was assessed in the prestudy and 12-month biopsies by in situ hybridization. The incidence of subsequent PCa was 11.6% in the flutamide group when compared with 30.2% in the placebo group over a follow-up period of 5 years (p = 0.0027). PSCA mRNA expression levels were significantly declined after treatment compared with that before treatment (p < 0.001). After treatment, 66 patients had reduced PSCA mRNA expression, in whom none was found with cancer on follow-up, however, 13 cases had increased PSCA mRNA expression levels, in whom 11 were found with cancer. Cox regression analysis demonstrated that HGPIN with increased PSCA mRNA expression after flutamide had an increased relative risk of 4.33 to develop subsequent cancer (95% confidence intervals: 2.48,7.36; p < 0.001). Seventeen (19.8%) cases had the flutamide-associated side effects, which were graded as mild, but all did not discontinue study. Flutamide can effectively and safely reduce PCa development and significantly suppress PSCA mRNA expression in men with isolated HGPIN, whereas the increased PSCA mRNA expression after therapy may be a clinically adverse predictor for cancer onset. © 2007 Wiley-Liss, Inc. [source] RM2 antigen (,1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Seiichi Saito Abstract Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, ,1,4-GalNAc-disialyl-Lc4, defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and ,4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern ,4, high Gleason score (,8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer. © 2005 Wiley-Liss, Inc. [source] Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Andrew H. Fischer Abstract Prostate cancer is still diagnosed by pathologists based on subjective assessment of altered cell and tissue structure. The cellular-level structural changes diagnostic of some forms of cancer are known to be induced by cancer genes, but the relation between specific cellular-level structural features and cancer genes has not been explored in the prostate. Two important cell structural changes in prostate cancer,nucleolar enlargement and nuclear envelope (NE) irregularity,are discussed from the perspective that they should also relate to the function of the genes active in prostate cancer. Enlargement of the nucleolus is the key diagnostic feature of high-grade prostatic intraepithelial neoplasia (PIN), an early stage that appears to be the precursor to the majority of invasive prostate cancers. Nucleolar enlargement classically is associated with increased ribosome production, and production of new ribosomes appears essential for cell-cycle progression. Several cancer genes implicated in PIN are known (in other cell types) to augment ribosome production, including c-Myc, p27, retinoblastoma, p53, and growth factors that impact on ERK signaling. However, critical review of the available information suggests that increased ribosome production per se may be insufficient to explain nucleolar enlargement in PIN, and other newer functions of nucleoli may therefore need to be invoked. NE irregularity develops later in the clonal evolution of some prostate cancers, and it has adverse prognostic significance. Nuclear irregularity has recently been shown to develop dynamically during interphase following oncogene expression, without a requirement for post-mitotic NE reassembly. NE irregularity characteristic of some aggressive prostate cancers could reflect cytoskeletal forces exerted on the NE during active cell locomotion. NE irregularity could also promote chromosomal instability because it leads to chromosomal asymmetry in metaphase. Finally, NE irregularity could impact replication competence, transcriptional programming and nuclear pore function. © 2003 Wiley-Liss, Inc. [source] Aurora-A over-expression in high-grade PIN lesions and prostate cancer,THE PROSTATE, Issue 4 2005Holly McKlveen Buschhorn Abstract BACKGROUND Over-expression of Aurora-A (Aurora 2 kinase, STK-15), a protein found in centrosomes thought to be associated with genetic instability, has been previously documented in prostate cancer [Pihan et al.: Cancer Res 61(5):2212,2219, 2001]. It is unknown if this protein is also over-expressed in high-grade prostatic intraepithelial neoplasia (PIN) lesions. METHODS PIN lesions were examined for increased Aurora-A using immunohistochemical staining on archival paraffin embedded prostatectomy tissue. Aurora-A expression was scored using size, number, and staining intensity. Protein expression was examined and compared between stromal cells, normal glands, high-grade PIN lesions, and invasive cancer. RESULTS Immunohistochemistry shows an increased expression of Aurora-A in 96% of high-grade PIN cases, and 98% in cancer lesions. Twenty-nine percent of cases of normal glands from cancerous prostates also showed increased Aurora-A expression. CONCLUSIONS Over-expression of Aurora-A is present in some normal and the majority of high-grade PIN lesions indicating that this may be an early event that leads to the genetic instability seen in prostate carcinogenesis. © 2005 Wiley-Liss, Inc. [source] Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: A histopathologic study of whole mount prostate specimensTHE PROSTATE, Issue 1 2004Karen Woodson Abstract BACKGROUND Gene methylation may contribute to prostate carcinogenesis through the silencing of gene transcription. We report on the methylation status of several genes shown to be silenced at different stages of progression using whole mount prostate specimens and laser capture microdissection. This is the first study to evaluate gene methylation patterns across multiple pre-cancerous and invasive cancer foci from the same prostate gland. METHODS Real-time PCR was used to evaluate methylation of five genes (GSTP1, RASSF1A, RAR,2, CD44, and EDNRB) across normal epithelium, high-grade prostatic intraepithelial neoplasia (HGPIN), and multiple tumor foci from each of 11 prostate cancer patients. RESULTS Gene methylation was not found in normal epithelium. To our knowledge, this is the first report of RASSF1A and RAR,2 methylation in HGPIN lesions (30% prevalence for each gene). In addition, RASSF1A, RAR,2, and GSTP1 methylation was highly prevalent in tumor foci (>75% for all three genes). Methylation of CD44 and EDNRB was observed in 41 and 38% of tumors but was not present in HGPIN. CONCLUSIONS These data suggest that genes may be methylated at different points in the histopathologic progression of prostate cancer and these differences can be found in various histologic foci from the same gland. © 2004 Wiley-Liss, Inc. [source] Contrast-enhanced colour Doppler-targeted vs a 10-core systematic repeat biopsy strategy in patients with previous high-grade prostatic intraepithelial neoplasiaBJU INTERNATIONAL, Issue 12 2010Michael Mitterberger Study Type , Diagnosis (case series) Level of Evidence 4 OBJECTIVE To compare the results of contrast-enhanced colour Doppler (CECD)-targeted prostate biopsy with a systematic 10-core grey-scale biopsy scheme in patients initially diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN), as although HGPIN is thought to be a precursor to invasive adenocarcinoma, its diagnosis is no longer considered an indication for repeat prostate biopsy and patients should be followed by prostate-specific antigen levels and a digital rectal examination. PATIENTS AND METHODS In all, 104 patients (aged 45,78 years) diagnosed with HGPIN on initial prostate needle biopsy were referred for a repeat biopsy within 6 months. Two independent examiners evaluated each patient; one used CECD-targeted biopsy (up to five cores) into hypervascular regions in the peripheral zone only, and subsequently the second took a systematic 10-core grey-scale biopsy. Cancer detection rates of both techniques were compared. RESULTS Overall, 26 of the 104 men (25%) had prostate cancer in the repeated biopsy. Using the CECD technique cancer was detected in 21% (22 of 104). The positive re-biopsy rate using the systematic technique was 9.6% (10 of 104; P < 0.001). The total incidence of HGPIN with no evidence of tumour on re-biopsy was 8.7% (nine of 104). The Gleason score in all 22 cancers detected with the CECD technique varied between 6 and 8. The systematic technique detected cancers with Gleason scores of 6 or 7. There were no adverse events or complications. CONCLUSION CECD increased the detection rate of prostate cancer, and using fewer biopsy cores than the systematic biopsy technique in patients previously diagnosed with HGPIN. [source] Detection rate and factors predictive the presence of prostate cancer in patients undergoing ultrasonography-guided transperineal saturation biopsies of the prostateBJU INTERNATIONAL, Issue 9 2010Giacomo Novara Study Type , Diagnostic (case series) Level of Evidence 4 OBJECTIVES To assess the prostate cancer detection rate and predictive factors for prostate cancer after transrectal ultrasonography (TRUS)-guided transperineal saturation re-biopsies of the prostate, using a 24-core scheme. PATIENTS AND METHODS We evaluated 143 consecutive patients undergoing TRUS-guided transperineal saturation re-biopsy of the prostate using a 24-core scheme. The inclusion criteria were a previous negative biopsy and a prostate-specific antigen (PSA) level of ,10.0 ng/mL, or of 4.0,10.0 ng/mL with a free/total ratio of <20% or an abnormal digital rectal examination or previous high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP). RESULTS The mean (sd) age of the patients was 66.5 (6.1) years and the median (interquartile range) PSA level was 9.0 (6.1,12.8) ng/mL. The number of previous biopsies was one in 59% of patients, two in 26% and three or more in 15%. We detected prostate cancer in 26%, ASAP in 5.6% and HGPIN in 2.1%. The cancer detection rate was 47%, 25.5% and 14% for prostate volumes of <40, 40,60 and ,60 mL, respectively (P = 0.002). On a multivariate analysis the total prostate volume (40,60 vs <40 mL, hazard ratio 5.683; >60 vs <40 mL, hazard ratio 6.965; P = 0.01) was the only significant predictor of prostate cancer at saturation biopsy. CONCLUSIONS TRUS-guided transperineal saturation re-biopsy of the prostate using a 24-core scheme resulted in a high cancer detection rate also in patients who had had two or more previous biopsies. The total prostate volume was the only predictor of prostate cancer. [source] The presence of prostate cancer on saturation biopsy can be accurately predictedBJU INTERNATIONAL, Issue 5 2010Sascha A. Ahyai Study Type , Diagnostic (non-consecutive) Level of Evidence 3b OBJECTIVE To improve the ability of our previously reported saturation biopsy nomogram quantifying the risk of prostate cancer, as the use of office-based saturation biopsy has increased. PATIENTS AND METHODS Saturation biopsies of 540 men with one or more previously negative 6,12 core biopsies were used to develop a multivariable logistic regression model-based nomogram, predicting the probability of prostate cancer. Candidate predictors were used in their original or stratified format, and consisted of age, total prostate-specific antigen (PSA) level, percentage free PSA (%fPSA), gland volume, findings on a digital rectal examination, cumulative number of previous biopsy sessions, presence of high-grade prostatic intraepithelial neoplasia on any previous biopsy, and presence of atypical small acinar proliferation (ASAP) on any previous biopsy. Two hundred bootstraps re-samples were used to adjust for overfit bias. RESULTS Prostate cancer was diagnosed in 39.4% of saturation biopsies. Age, total PSA, %fPSA, gland volume, number of previous biopsies, and presence of ASAP at any previous biopsy were independent predictors for prostate cancer (all P < 0.05). The nomogram was 77.2% accurate and had a virtually perfect correlation between predicted and observed rates of prostate cancer. CONCLUSIONS We improved the accuracy of the saturation biopsy nomogram from 72% to 77%; it relies on three previously included variables, i.e. age, %fPSA and prostate volume, and on three previously excluded variables, i.e. PSA, the number of previous biopsy sessions, and evidence of ASAP on previous biopsy. Our study represents the largest series of saturation biopsies to date. [source] The proportion of cores with high-grade prostatic intraepithelial neoplasia on extended-pattern needle biopsy is significantly associated with prostate cancer on site-directed repeat biopsyBJU INTERNATIONAL, Issue 4 2007Ardavan Akhavan OBJECTIVE To determine whether the predictive value of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) for an unsampled prostate cancer on an extended biopsy is lower due to more thorough prostate sampling, and whether the proportion of cores with HGPIN is associated with prostate cancer, as isolated HGPIN on sextant prostate biopsy is associated with a 27,57% risk of prostate cancer on repeat biopsy. PATIENTS AND METHODS All extended prostate biopsies taken by one urologist over 6 years were reviewed for patients with isolated HGPIN on initial biopsy. Biopsies were evaluated for histological features and the proportion of cores with HGPIN. The clinical characteristics and pathological findings from subsequent biopsies were determined. RESULTS Of 577 men having extended biopsies, 48 had isolated HGPIN, followed by one to four site-directed repeat biopsies. Although only 10 (21%) had cancer on the first repeat biopsy, overall 15 (31%) had cancer. Those with cancer on repeat biopsy had a significantly higher proportion of cores with HGPIN, i.e. 29% vs 15%, cancer vs no cancer, respectively (P = 0.04). CONCLUSIONS Isolated HGPIN on extended biopsy conferred a 31% risk of unsampled prostate cancer. The proportion of cores with HGPIN on initial biopsy was significantly associated with the risk of cancer. The same was not true for age, race, prostate-specific antigen level, or the findings on digital rectal examination. The significant association between the proportion of cores with HGPIN and the risk of cancer suggests that patients with unifocal HGPIN on extended biopsy be managed expectantly, whereas those with multifocal HGPIN be re-biopsied. [source] The incidence of high-grade prostatic intraepithelial neoplasia and atypical glands suspicious for carcinoma on first-time saturation needle biopsy, and the subsequent risk of cancerBJU INTERNATIONAL, Issue 4 2007Lynn Schoenfield OBJECTIVE To investigate the detection rate and extent of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands (AG) suspicious for prostate cancer, and the cancer risk in subsequent biopsies, diagnosed by a first 24-core saturation biopsy, as although the optimum extent of biopsy is controversial there is a trend to increase the number of cores taken, and apart from detecting prostate cancer, identifying HGPIN and AG is associated with a greater risk of finding cancer in subsequent biopsies, thus warranting a closer follow-up. PATIENTS AND METHODS The study included 100 men with consecutive first-time saturation biopsies; the indications for biopsy were an abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level of >2.5 ng/mL. Each biopsy specimen was reviewed retrospectively by two pathologists to confirm the histological diagnosis. The number and percentage of cores positive for HGPIN, bilateral involvement and multifocality (HGPIN involving two or more cores) were recorded in each case. The presence of AG and cancer was also recorded. An extended (10,12 cores) repeat biopsy was available in 23 patients. RESULTS The median (range) age and PSA level of the patients was 63 (41,80) years and 4.9 (1.5,67.0) ng/mL, respectively. Of the 100 patients, 34% had normal findings (benign prostatic tissue, BPT), 39% had cancer, 26% had HGPIN and cancer, 22% had HGPIN alone, and 5% had AG. Repeat biopsies were available in nine of the 22 (41%) patients with HGPIN, four of five with AG, and 10 of the 34 (29%) with BPT. The median (range) interval between the first and second biopsy was 13 (4,36) months. Prostate cancer was detected at the second biopsy in a third of patients with isolated HGPIN on the first biopsy, and one of the four with AG. None of the patients with BPT had cancer on re-biopsy. The cancer detection rate was significantly greater in patients with multifocal than in those with unifocal HGPIN (80% vs none, P = 0.010). The median number of cores and percentage of tissue involved by HGPIN was 3.5 (2,5) and 1.0 (0.5,1.2)%, respectively, in patients with cancer detected in repeat biopsies, compared to 1.0 (1,3) and 0.2 (0.2,0.6)% in patients without cancer on repeat biopsy (P = 0.023 and 0.015, respectively). CONCLUSION Identifying multifocal HGPIN on first saturation biopsy is associated with an overall cancer detection rate of 80% on repeat 10,12-core biopsy. Although there were few patients, the detection of multifocal HGPIN warrants additional searches for concurrent invasive carcinoma by repeated biopsy. [source] Do all patients with high-grade prostatic intraepithelial neoplasia on initial prostatic biopsy eventually progress to clinical prostate cancer?BJU INTERNATIONAL, Issue 4 2006MUSTAFA SOFIKERIM No abstract is available for this article. [source] | ||||||||||